Decitabine in the Treatment of Acute Myeloid Leukemia and Myelodysplastic Syndromes, Which Combined with Complex Karyotype Respectively

Abstract

Background:We conducted a study exploring the clinical safety and efficacy of decitabine in patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), combined with a complex karyotype. Materials and Methods: From April 2009 to September 2013, a total of 35 patients with AML/MDS combined with a complex karyotype diagnosed in the First Affiliated Hospital of Soochow University were included for retrospective analysis. All patients were treated with decitabine alone (20mg/m 2 daily for 5 days) or combination AAG chemotherapy (Acla 20mg qod*4d, Ara-C 10mg/m 2 q12h*7d, G-CSF 300μg qd, the dose of G-CSF adjusted to the amount in blood routinely). Results: In 35 patients, 15 exhibited a complete response (CR), and 6 a partial response (PR), the overall response rate (CR+PR) being 60% (21 of 35). Median disease-free survival was 18 months and overall survival was 14 months. In the 15 MDS patients with a complex karyotype, the CR rate was 53.3% (8 of 15); in 20 AML patients with complex karyotype, the overall response rate was 65% (13 of 20). The response rate of decitabine alone (22 cases) was 56.5% (13 of 22), while in the combination chemotherapy group (13 cases), the effective rate was 61.5% (8 of 13)(P>0.05). There are 15 patients with chromosome 7 aberration, after treatment with decitabine, 7 CR, 3 PR, overall response rate was 66.7% (10 of 15). Of 18 patients with 3 to 5 kinds of chromosomal abnormalities, 66.7% demonstrated a response; of 17 with more than 5 chromosomal abnormalities, 52.9% had a response. In the total of 35 patients, with one course (23 patients) and ≥two courses (12 patients), the overall response rate was 40.9% and 92.3% (P<0.05). Grade Ⅲ to IV hematological toxicity was observed in 27 cases (75%). Grade Ⅲ to IV infections were clinically documented in 7 (20%). Grades Ⅰ to Ⅱ non-hematological toxicity were infections (18 patients), haematuria (2 patients), and bleeding (3 patients). With follow-up until September 2013, 7 patients were surviving, 18 had died and 10 were lost to follow-up. In the 6 cases who underwent allogeneic hematopoietic stem cell transplantation (HSCT) all were still relapse-free survivors. Conclusions: Decitabine alone or combination with AAG can improve outcome of AML/MDS with a complex karyotype, there being no significant difference decitabine in inducing remission rates in patients with different karyotype. Increasing the number of courses can improve efficiency. This approach with fewer treatment side effects in patients with a better tolerance should be employed in order to create an improved subsequent chance for HSCT.

TP53 mutations predict decitabine‐induced complete responses in patients with myelodysplastic syndromes

“…In our study, TP53 mutations were associated with increases in CRs to DAC therapy, particularly in individuals with TP53 mutations and complex karyotypes (involving abnormalities on chromosomes 5 and/or 7 or containing monosomies) (Table S3). Other studies (Gao et al, 2015;Lubbert et al, 2016) have reported higher levels of responsiveness toward DAC among MDS patients with poor karyotypes (complex karyotypes, chromosome 7 abnormalities, or monosomies). Because TP53 mutations frequently coincide with complex karyotypes, it is understandable that MDS patients with TP53 mutations are especially sensitive to DAC therapy.…”

Adult Primary Myelodysplastic Syndrome: Experience from a Tertiary Care Center in Pakistan

“…Myelodysplasia is a heterogeneous disease with an increased risk of leukemic transformation, overall 40% of patients will transform to AML during the disease course (Chevassut et al, 2011;Gao et al, 2015).…”

Decitabine priming prior to low-dose chemotherapy improves patient outcomes in myelodysplastic syndromes-RAEB: a retrospective analysis vs. chemotherapy alone

“…Previous studies suggested that decitabine monotherapy is a better choice for MDS patients with poor karyotypes (Li et al 2013; Lubbert et al 2001; Wu et al 2016). Several studies showed that decitabine in combination with CAG could achieve 50–70% CR in AML and MDS patients with complex karyotypes (Gao et al 2015; Li et al 2015). Gao et al also noted an association of treatment response with the number of courses in AML and MDS patients with complex karyotypes (Gao et al 2015).…”

“…Several studies showed that decitabine in combination with CAG could achieve 50–70% CR in AML and MDS patients with complex karyotypes (Gao et al 2015; Li et al 2015). Gao et al also noted an association of treatment response with the number of courses in AML and MDS patients with complex karyotypes (Gao et al 2015). Patients with poor karyotypes who received decitabine in combination with CAG tended to have a longer OS (Li et al 2015).…”

“…In patients receiving decitabine monotherapy, the rate of CR and overall response (OR) has been reported to be 13–39 and 32–70%, respectively (Iastrebner et al 2010; Kantarjian et al 2007a, c; Lee et al 2011; Oki et al 2012; Steensma et al 2009). Decitabine in combination with a variety of agents, including histone deacetylase inhibitors, thalidomide, and conventional chemotherapeutics, has been developed to treat intermediate- and high-risk MDS and AML (Blum et al 2007; Daver et al 2016; Gao et al 2015; Garcia-Manero et al 2006; Geng et al 2016; Jiang et al 2015; Kirschbaum et al 2014; Li et al 2015; Song et al 2012; Yang et al 2005; Zhao et al 2015). Several studies showed that decitabine in combination with chemotherapy improved the outcomes in patients with relapsed/refractory AML or AML transformed from MDS (MDS/AML) (Leonard et al 2014; Li et al 2015; Scandura et al 2011; Song et al 2012).…”